Watson CIT - SWIG Boardroom (CIT241)

The importance of translational regulation in gene expression and function is increasingly appreciated. With the goal of prospectively defining translational regulatory programs underlying epithelial to mesenchymal transition (EMT), we utilized polyribosomal profiling to examine breast epithelial cells undergoing this process. We found ten translationally regulated drivers of EMT, each possessing a GU-rich cis-element within the 3’ untranslated region (UTR) of their mRNA. These cis-elements are necessary for the translational regulation imparted by these 3’ UTRs, and are directly bound by the CELF1 protein. Interestingly, CELF1 itself is regulated post-translationally during the EMT program, and is both necessary and sufficient for both mesenchymal transition and tumor progression in a xenograft model. In human breast cancer tissues, CELF1 protein, but not mRNA, is significantly overexpressed. Our data define an eleven component genetic pathway driving EMT and ultimately tumor progression that is completely invisible in standard transcriptional profiling data.